Unraveling the molecular pathophysiology of myelodysplastic syndromes Journal Article


Authors: Bejar, R.; Levine, R.; Ebert, B. L.
Article Title: Unraveling the molecular pathophysiology of myelodysplastic syndromes
Abstract: Somatically acquired genetic abnormalities lead to the salient features that define myelodysplastic syndromes (MDS): clonal hematopoiesis, aberrant differentiation, peripheral cytopenias, and risk of progression to acute myeloid leukemia. Although specific karyotypic abnormalities have been linked to MDS for decades, more recent findings have demonstrated the importance of mutations within individual genes, focal alterations that are not apparent by standard cytogenetics, and aberrant epigenetic regulation of gene expression. The spectrum of genetic abnormalities in MDS implicates a wide range of molecular mechanisms in the pathogenesis of these disorders, including activation of tyrosine kinase signaling, genomic instability, impaired differentiation, altered ribosome function, and changes in the bone marrow microenvironment. Specific alterations present in individual patients with MDS may explain much of the heterogeneity in clinical phenotype associated with this disease and can predict prognosis and response to therapy. Elucidation of the full complement of genetic causes of MDS promises profound insight into the biology of the disease, improved classification and prognostic scoring schemes, and the potential for novel targeted therapies with molecular predictors of response.
Keywords: signal transduction; acute granulocytic leukemia; chronic myelomonocytic leukemia; gene mutation; gene translocation; mutation; dna-binding proteins; proto-oncogene proteins; janus kinase 2; review; stem cell factor; gene expression; bone marrow; genetic association; cytogenetics; enzyme activation; protein tyrosine kinase; protein p53; chromosome aberration; myelodysplastic syndrome; epigenesis, genetic; genomic instability; gene control; microenvironment; wt1 protein; chromosome aberrations; flt3 ligand; immunosuppressive treatment; k ras protein; chromosome deletion; genetic screening; repressor proteins; apc protein; chromosome 12q; protein tyrosine phosphatase shp 2; chromosome 11q; myelodysplastic syndromes; chromosome 17q; genes, p53; chromosome 20q; chromosome 7q; chromosome 7; y chromosome; transcription factor runx1; molecular pathology; chromosome 9q; transcription factor ezh2; guanosine triphosphatase; oncogene n ras; nucleophosmin; chromosome 13q; chromosome 5q; early growth response factor 1; nicotinamide adenine dinucleotide phosphate; chromosome deletion y; juvenile myelomonocytic leukemia; trisomy 8
Journal Title: Journal of Clinical Oncology
Volume: 29
Issue: 5
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2011-02-10
Start Page: 504
End Page: 515
Language: English
DOI: 10.1200/jco.2010.31.1175
PUBMED: 21220588
PROVIDER: scopus
PMCID: PMC3969457
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 23 June 2011" - "CODEN: JCOND" - "Source: Scopus"
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MSK Authors
  1. Ross Levine
    469 Levine